Association of Dual Antiplatelet Therapy With Ticagrelor With Vein Graft Failure After Coronary Artery Bypass Graft Surgery
Authors: Sigrid Sandner, Björn Redfors, Dominick J. Angiolillo, Katia Audisio, Stephen E. Fremes, Paul W.A. Janssen, Alexander Kulik, Roxana Mehran, Joyce Peper, Marc Ruel, Jacqueline Saw, Giovanni Jr Soletti, Andrew Starovoytov, Jurrien M. ten Berg, Laura M. Willemsen, Qiang Zhao, Yunpeng Zhu, Mario Gaudino
Journal: JAMA (2022)

<h3>Importance</h3> The role of ticagrelor with or without aspirin after coronary artery bypass graft surgery remains unclear. <h3>Objective</h3> To compare the risks of vein graft failure and bleeding associated with ticagrelor dual antiplatelet therapy (DAPT) or ticagrelor monotherapy vs aspirin among patients undergoing coronary artery bypass graft surgery. <h3>Data Sources</h3> MEDLINE, Embase, and Cochrane Library databases from inception to June 1, 2022, without language restriction. <h3>Study Selection</h3> Randomized clinical trials (RCTs) comparing the effects of ticagrelor DAPT or ticagrelor monotherapy vs aspirin on saphenous vein graft failure. <h3>Data Extraction and Synthesis</h3> Individual patient data provided by each trial were synthesized into a combined data set for independent analysis. Multilevel logistic regression models were used. <h3>Main Outcomes and Measures</h3> The primary analysis assessed the incidence of saphenous vein graft failure per graft (primary outcome) in RCTs comparing ticagrelor DAPT with aspirin. Secondary outcomes were saphenous vein graft failure per patient and Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding events. A supplementary analysis included RCTs comparing ticagrelor monotherapy with aspirin. <h3>Results</h3> A total of 4 RCTs were included in the meta-analysis, involving 1316 patients and 1668 saphenous vein grafts. Of the 871 patients in the primary analysis, 435 received ticagrelor DAPT (median age, 67 years [IQR, 60-72 years]; 65 women [14.9%]; 370 men [85.1%]) and 436 received aspirin (median age, 66 years [IQR, 61-73 years]; 63 women [14.5%]; 373 men [85.5%]). Ticagrelor DAPT was associated with a significantly lower incidence of saphenous vein graft failure (11.2%) per graft than was aspirin (20%; difference, −8.7% [95% CI, −13.5% to −3.9%]; OR, 0.51 [95% CI, 0.35 to 0.74];<i>P</i> &lt; .001) and was associated with a significantly lower incidence of saphenous vein graft failure per patient (13.2% vs 23.0%, difference, −9.7% [95% CI, −14.9% to −4.4%]; OR, 0.51 [95% CI, 0.35 to 0.74];<i>P</i> &lt; .001). Ticagrelor DAPT (22.1%) was associated with a significantly higher incidence of BARC type 2, 3, or 5 bleeding events than was aspirin (8.7%; difference, 13.3% [95% CI, 8.6% to 18.0%]; OR, 2.98 [95% CI, 1.99 to 4.47];<i>P</i> &lt; .001), but not BARC type 3 or 5 bleeding events (1.8% vs 1.8%, difference, 0% [95% CI, −1.8% to 1.8%]; OR, 1.00 [95% CI, 0.37 to 2.69];<i>P</i> = .99). Compared with aspirin, ticagrelor monotherapy was not significantly associated with saphenous vein graft failure (19.3% vs 21.7%, difference, −2.6% [95% CI, −9.1% to 3.9%]; OR, 0.86 [95% CI, 0.58 to 1.27];<i>P</i> = .44) or BARC type 2, 3, or 5 bleeding events (8.9% vs 7.3%, difference, 1.7% [95% CI, −2.8% to 6.1%]; OR, 1.25 [95% CI, 0.69 to 2.29];<i>P</i> = .46). <h3>Conclusions and Relevance</h3> Among patients undergoing coronary artery bypass graft surgery, adding ticagrelor to aspirin was associated with a significantly decreased risk of vein graft failure. However, this was accompanied by a significantly increased risk of clinically important bleeding.